Patents Assigned to Gradalis, Inc.
  • Publication number: 20120231537
    Abstract: The present disclosure generally relates to highly pure plasmid compositions having low, or undetectable, levels of colanic acid and other contaminants made by a process that comprises purifying plasmid DNA by chromatography, treating the purified plasmid DNA with a polypeptide that digests colanic acid under conditions that digest the colonic acid, and separating the plasmid DNA from the digested colonic acid.
    Type: Application
    Filed: March 27, 2012
    Publication date: September 13, 2012
    Applicant: Gradalis, Inc.
    Inventors: Nancy Smyth Templeton, Li Chen
  • Publication number: 20120232268
    Abstract: Monovalent compounds having moieties comprising at least one amino acid side chain are bound to a core molecule, which also comprises a nucleophilic moiety bound to said core molecule. Monovalent compounds also comprise a macrocyclic ring, a nucleophilic moiety, and a spacer group. Monovalent compounds may be combined into bivalent and trivalent compounds, some of which may have a labeling tag. Methods of production of bivalent compounds and contemplated uses thereof are disclosed.
    Type: Application
    Filed: March 13, 2012
    Publication date: September 13, 2012
    Applicant: GRADALIS, INC.
    Inventor: Kevin Burgess
  • Patent number: 8252526
    Abstract: The present invention relates to certain novel shRNA molecules and methods of use thereof. According to certain embodiments of the present invention, methods for reducing the expression level of a target gene are provided. Such methods generally comprise providing a cell with one or more precursor nucleic acid sequences that encode two or more RNA molecules. A first RNA molecule comprises a double stranded sequence, which includes a guide strand sequence that is complementary to a portion of an mRNA transcript encoded by the target gene. In addition, a second RNA molecule comprises a second double stranded sequence, which includes a second guide strand sequence that is partially complementary to a portion of the mRNA transcript encoded by the target gene. Preferably, the second guide strand sequence comprises one or more bases that are mismatched with a nucleic acid sequence of the mRNA transcript encoded by the target gene.
    Type: Grant
    Filed: November 9, 2007
    Date of Patent: August 28, 2012
    Assignee: Gradalis, Inc.
    Inventor: Donald Rao
  • Publication number: 20120183955
    Abstract: A method for designing a bi-shRNA expression cassette encoding a bi-shRNA comprising: selecting one or more target site sequences; providing a backbone sequence comprising a first and a second stem-loop structure, inserting a first passenger strand and a second passenger strand and providing for synthesis of the bi-shRNA expression cassette.
    Type: Application
    Filed: February 1, 2012
    Publication date: July 19, 2012
    Applicant: GRADALIS, INC.
    Inventor: Donald Rao
  • Publication number: 20110286979
    Abstract: Compositions and methods of augmenting the anti-tumor activities of docetaxel and other taxanes by combination with a bi-functional small hairpin RNA (bi-shRNA) is described herein. The instant invention describes the interactive outcome of STMN1 knockdown with docetaxel. In vitro docetaxel (DOC) dose response assessments with or without co-treatment with bi-shRNASTMN1 in CCL-247 and SK-MEL-28 melanoma cells indicated that STMN1 knockdown significantly reduced DOC concentration needed to inhibit cancer cell growth by 50% (IC50) of CCL-247 cells from 1.8±0.2 to 0.6±0.4 nm (n=3, p<0.05), and SK-MEL-28 cells from 1.7±0.2 nm to 0.1±0.0 (n=3, p<0.05). The 3- to >10-fold reduction in DOC IC50 suggest that bi-shRNASTMN1 can markedly enhance the effectiveness of docetaxel for human cancer cells.
    Type: Application
    Filed: May 19, 2011
    Publication date: November 24, 2011
    Applicant: GRADALIS, INC.
    Inventors: Alex W. Tong, Yu Yang, Donald Rao, Phillip B. Maples, Neil Senzer, John J. Nemunaitis, Zhaohui Wang
  • Publication number: 20110262408
    Abstract: Compositions and methods for cancer treatment are discloses herein. More specifically the present invention describes an autologous cancer vaccine genetically modified for Furin knockdown and GM-CSF expression. The vaccine described herein attenuates the immunosuppressive activity of TGF-? through the use of bi-functional shRNAs to knock down the expression of furin in cancer cells, and to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
    Type: Application
    Filed: December 20, 2010
    Publication date: October 27, 2011
    Applicant: GRADALIS, INC.
    Inventors: John J. Nemunaitis, Neil Senzer, Phillip B. Maples, Donald Rao
  • Publication number: 20110150832
    Abstract: Compositions and methods to attenuate the immunosuppressive activity of TGF-? through the use of bi-functional shRNAs is described herein. The bi-functional shRNAs of the present invention knocks down the expression of furin in cancer cells to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
    Type: Application
    Filed: December 20, 2010
    Publication date: June 23, 2011
    Applicant: GRADALIS, INC.
    Inventors: John J. Nemunaitis, Neil Senzer, Phillip B. Maples, Donald Rao
  • Publication number: 20110117183
    Abstract: A bifunctional shRNA-based composition and methods for knocking down the expression of the PDX-1 oncogene in target cells is described herein. The invention also provides methods to deliver the shRNA-containing expression vectors to target tissues overexpressing the PDX-1 oncogene.
    Type: Application
    Filed: October 27, 2010
    Publication date: May 19, 2011
    Applicant: GRADALIS, INC.
    Inventors: John J. Nemunaitis, Donald Rao, F. Charles Brunicardi
  • Publication number: 20110081403
    Abstract: The present invention provides reconstituted histone octamers with multiple modifications (e.g. acetylation of all histones and trimethylation of histone H3K4) assembled onto plasmids for increased transcription post-transfection using our unique bi-lamellar invaginated liposomes (BIVs) to more effectively recruit the transcriptional machinery of human cancer cells post-transfection and substantially increase the production of therapeutic gene products.
    Type: Application
    Filed: September 22, 2010
    Publication date: April 7, 2011
    Applicant: GRADALIS, INC.
    Inventor: Nancy Smyth Templeton
  • Publication number: 20110059161
    Abstract: Compositions and methods for tissue-specific targeted delivery of therapeutic agents through the use of tissue-specific peptidomimetic ligands are disclosed herein. The ligand comprises a composition of formula A-scaffold-A? and one or more hydrophobic anchors covalently linked to the scaffold. The A and A? compounds linked to the scaffold comprise monovalent peptidomimetic compounds wherein each monovalent peptidomimetic compound is selected from the group consisting of fragments IKs, GKs, IDs, GSs, GTs, VSs, TKs, KTs, ARs, KIs, KEs, AEs, GRs, YSs, IRs, and morpholino.
    Type: Application
    Filed: September 3, 2010
    Publication date: March 10, 2011
    Applicant: GRADALIS, INC.
    Inventor: Nancy Smyth Templeton
  • Publication number: 20110027373
    Abstract: According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.
    Type: Application
    Filed: February 7, 2008
    Publication date: February 3, 2011
    Applicant: GRADALIS, INC.
    Inventors: Phillip Maples, Chris Jay, John J. Nemunaitis
  • Publication number: 20110020924
    Abstract: The present disclosure generally relates to highly pure plasmid compositions having low, or undetectable, levels of colanic acid and other contaminants. The compositions described herein have a range of uses, including diverse applications in the field of bioterrorism, environmental science, food science, forensics, molecular biology, and health and medicine.
    Type: Application
    Filed: April 30, 2009
    Publication date: January 27, 2011
    Applicant: GRADALIS, INC.
    Inventor: Nancy Smyth Templeton
  • Publication number: 20100166845
    Abstract: In certain embodiments, the invention provides methods for treating cancer, comprising: (a) obtaining a specimen of cancer tissue and normal tissue from a patient; (b) extracting total protein and RNA from the cancer tissue and normal tissue; (c) obtaining a protein expression profile of the cancer tissue and normal tissue; (d) identifying over-expressed proteins in the cancer tissue; (e) comparing the protein expression profile to a gene expression profile; (f) identifying at least one prioritized protein target by assessing connectivity of each said over-expressed protein to other cancer-related or stimulatory proteins; (g) designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding the prioritized target protein; (h): designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding a protein of higher priority in the signaling pathway in which the first protein is a component; (i) incorporating the first cass
    Type: Application
    Filed: October 30, 2009
    Publication date: July 1, 2010
    Applicant: GRADALIS, INC.
    Inventors: David Shanahan, John Nemunaitis, Neil Senzer, Phillip Maples, Donald Rao
  • Publication number: 20100075404
    Abstract: The present disclosure generally relates to processes employing polypeptides having colanic acid-degrading activity. The processes generally involve contacting a biological material with a polypeptide capable of digesting colanic acid. Additional process steps, such as chromatographic separation steps, are also described.
    Type: Application
    Filed: April 30, 2009
    Publication date: March 25, 2010
    Applicant: GRADALIS, INC.
    Inventor: Nancy Smyth Templeton
  • Publication number: 20090275088
    Abstract: The present disclosure generally relates to processes for preparing highly pure plasmid compositions. The processes generally involve treating a composition comprising plasmid DNA with a polypeptide to digest colanic acid. The treated plasmid DNA is then separated from the treated composition.
    Type: Application
    Filed: April 30, 2009
    Publication date: November 5, 2009
    Applicant: GRADALIS, INC.
    Inventor: Nancy Smyth Templeton
  • Publication number: 20090275122
    Abstract: The present disclosure generally relates to polypeptides having colanic acid-degrading activity and methods of using the same. Polynucleotides encoding such polypeptides are also described. The polypeptides may be used, for example, in processes for degrading colanic acid, processes for the removal of endotoxins from biological samples, and processes for purifying plasmid DNA.
    Type: Application
    Filed: April 30, 2009
    Publication date: November 5, 2009
    Applicant: GRADALIS, INC.
    Inventor: Nancy Smyth Templeton